1. Field of the Invention
This invention relates to a monoclonal anti-idiotypic antibody, a hybridoma producing the antibody, and use thereof.
The monoclonal anti-idiotypic antibody which is provided by the present invention is specific to the human IgG.sub.1 type monoclonal antibody specific to nicotinic acetylcholine receptor. It is, therefore, useful in the diagnosis and treatment of myasthenia gravis which is characterized mainly by impairment of neuromuscular transmission caused by the presence of autoantibodies against the nicotinic acetylcholine receptor present on the post-synaptic membrane of the neuromuscular junction.
2. Prior Art Statement
It is reported in European Journal of Immunology, Vol. 12, pages 790-792 (1982) that one of the hybridoma strains acquired by immunizing a BALB/c mouse with the heavy chain part of an antigen-binding fragment (Fab) originating in the IgG.sub.3 of the serum from a patient of myasthenia gravis, fusing the spleen cells collected from the immunized BALB/c mouse with a cell line SP2/0-Ag14 of B lymphocytoma thereby producing a hybridoma, and then cloning the hydridoma is capable of yielding a monoclonal anti-idiotypic antibody to the antibody against the nicotinic acetylcholine receptor originating in the patient of myasthenia gravis. In Nature, Vol. 301, pages 611-614 (1983), it is reported that the cell line obtained by fusing the peripheral blood lymphocyte of a patient of myasthenia gravis with the variant, GK-5, of B cell produce a human monoclonal antibody possessing a .mu. chain as a heavy chain and a .kappa. chain as a light chain and PG,3 that the human monoclonal antibody produced by the cell line is presumed to be an anti-idiotypic antibody against the antibody to the nicotinic acetylcholine receptor. Japanese Patent Public Disclosure SHO 56(1981)-128722 states that an antibody against the antibody to the acetylcholine receptor was obtained by immunizing a rabbit with an antibody against the acetylcholine receptor obtained from the serum of a patient of myasthenia gravis, isolating an immunoglobulin by fractionation from the antiserum taken from the immunized rabbit, and subjecting the immunoglobulin to affinity chromatography using a Sepharose having immobilized thereon an antibody to the acetylcholine receptor. It also discloses a method for the removal of an antibody against the acetylcholine receptor, which method comprises preparing a material for removal of an antibody against the acetylcholine receptor by immobilizing on an organic or inorganic carrier an antibody to the aforementioned antibody against the acetylcholine receptor and causing this material to contact a body fluid containing an antibody against the acetylcholine receptor.
The method reported in European Journal of Immunology can be hardly called a practical approach inasmuch as the autoantibody against the nicotinic acetylcholine receptor is present only in a very minute amount in the IgG.sub.3 which gives rise to the heavy chain part of the antigen-binding fragment. The method which is reported in Nature is not a practical approach either since the lymphocyte capable of producing an anti-idiotypic antibody to the antibody against the nicotinic acetylcholine receptor is present only in a trace amount in the peripheral blood lymphocyte of a patient of myasthenia gravis. The method which is disclosed in Japanese Patent Public Disclosure SHO 56(1981)-128722 cannot be called practical because the antibody against the acetylcholine receptor is present only in a very minute amount in the serum of a patient of myasthenia gravis and further because the antibody to the antibody against the acetylcholine receptor is present only in a negligibly small amount in the antiserum obtained by immunizing a rabbit with an antibody against the acetycholine receptor. Further, the material for the removal of the antibody against the acetycholine receptor does not easily acquire uniform quality because the antibody to the antibody against the acetylcholine receptor to be contained in the removing material varies in nature depending on particular rabbit immunized with the antibody.